Cell surfaces of both normal and tumor cells are characterized by a plethora of carbohydrate structures resulting from the glycosylation of lipids and proteins. In general, it is recognized that the glycosylation patterns exhibited by tumor cells and by normal cells are markedly different. More than a dozen tumor-associated glycosydic structures, including Le.sup.a, sialyl-Le.sup.a, Le.sup.x, and sialyl-Le.sup.x have been described. It is also characteristic of the transition from normal to transformed (tumor) cell that the size of asparagine linked (N-linked) oligosaccharides is markedly increased, and occurrence of high molecular weight fucosylated N-linked oligosaccharides is a reproducible correlate with malignant transformation.
In particular, it has been shown that there is a correlation between the degree of increase in beta(1-6) branching of N-linked oligosaccharides and the metastatic potential of murine and human tumor cells (Dennis, J. W., Cancer Surveys (1988) in press; Dennis, J. W., et al, Science (1987) 236:582).
It has also been shown that tumor cell mutants deficient in GnT-V, and therefore in the large, highly branched cell surface carbohydrates are dramatically decreased in their metastatic potential (Dennis, J. W., et al, Science (1987) 236:582 (supra)). Studies on BHK cells transformed with the polyoma DNA papovavirus, or with the RNA retrovirus Rous sarcoma virus, showed that transformation resulted in an increase in branching at the glycosylation acceptor trisaccharide portion of the glycoside, beta-GlcNAc(1-2)alpha-Man(1-6)beta-Man.fwdarw.(Yamashida, K., et al, J Biol Chem (1984) 259:10834; Yamashida, K., et al, J Biol Chem (1985) 260:3963; Pierce, M., et al, J Biol Chem (1986) 261:10772).
The increase in branching at this trisaccharide portion was correlated with an increase in the activity of N-acetyl glucosaminyl transferase-V (GnT-V, EC 2.4.1.155), which catalyzes the branching of the foregoing trisaccharide portion contained in N-linked carbohydrates by transfer of an acetyl glucosamine residue from UDP-GlcNAc into a 1-6 linked branch with the alpha-mannosyl residue of this trisaccharide portion in the context of Reaction Scheme I (Cumming, R. D., et al, J Biol Chem (1982) 257:11230). ##STR1##